DEXAMETHASONE SODIUM PHOSPHATE - dexamethasone sodium

phosphate injection, suspension

General Injectables & Vaccines
---------Dexamethasone Sodium Phosphate 4 mg/mL Injection, USP 30 mL Multi Dose
Vial

Description
Dexamethasone Sodium Phosphate Injection, USP is a water-soluble inorganic
ester of dexamethasone.
It occurs as a yellow crystalline powder, is odorless or has a slight odor of alcohol,
is exceedingly hygroscopic, and is freely soluble in water.
Dexamethasone Sodium Phosphate Injection, USP is a synthetic adrenocortical
steroid anti-inflammatory drug.
It has the following structural formula:

Dexamethasone Sodium Phosphate Injection, USP C22H28FNa2O8P, has a

molecular weight of 516.41 and the chemical name 9- fluoro-11b,17,21trihydroxy-16a-methylpregna-1,4-diene-3,20-dione 21-(dihydrogen phosphate)
disodium salt. Dexamethasone Sodium Phosphate Injection, USP 4 mg/mL is a
sterile solution for intravenous, intramuscular, intra-articular, intralesional and soft
tissue administration.
Each mL of the injection contains the following components:
Dexamethasone Sodium Phosphate
(equivalent to 4 mg of Dexamethasone Phosphate)...4.37 mg
Sodium Sulfite.............................................................1 mg

Benzyl Alcohol.............................................................10 mg
Sodium Citrate.............................................................for isotonicity
Water for Injection........................................................q.s.
pH adjusted between 7.5 and 10.5 with Citric Acid and/or Sodium Hydroxide.

Clinical Pharmacology
Dexamethasone Sodium Phosphate Injection, USP has a rapid onset but short
duration of action when compared with less soluble preparations. Because of this,
it is suitable for the treatment of acute disorders responsive to adrenocortical
steroid therapy. Naturally occurring glucocorticoids (hydrocortisone and
cortisone), which also have salt-retaining properties, are used as replacement
therapy in adrenocortical deficiency states. Their synthetic analogs, including
dexamethasone, are primarily used for their potent antiinflammatory effects in
disorders of many organ systems. Glucocorticoids cause profound and varied
metabolic effects. In addition, they modify the body's immune responses to diverse
stimuli. At equipotent anti-inflammatory doses, dexamethasone almost completely
lacks the sodium-retaining property of hydrocortisone and closely related
derivatives of hydrocortisone.

Indications and Usage

1. By intravenous or intramuscular injection when oral therapy is not feasible:
1. Endocrine disorders
Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone
is the drug of choice; synthetic analogs may be used in conjunction with
mineralocorticoids where
applicable; in infancy, mineralocorticoid
supplementation is of particular importance)
Acute adrenocortical insufficiency (hydrocortisone or cortisone is the drug of
choice; mineralocorticoid supplementation may be necessary, particularly when
synthetic analogs are used)
Preoperatively, and in the event of serious trauma or illness, in patients with
known adrenal insufficiency or when adrenocortical reserve is doubtful
Shock unresponsive to conventional therapy if adrenocortical insufficiency
exists or is suspected
Congenital adrenal hyperplasia
Nonsuppurative thyroiditis
Hypercalcemia associated with cancer
2. Rheumatic disorders
As adjunctive therapy for short-term administration (to tide the patient over an
acute episode or exacerbation) in:

Post-traumatic osteoarthritis
Synovitis of osteoarthritis
Rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may
require low-dose maintenance therapy)
Acute and subacute bursitis
Epicondylitis
Acute nonspecific tenosynovitis
Acute gouty arthritis
Psoriatic arthritis
Ankylosing spondylitis
3. Collagen diseases
During an exacerbation or as maintenance therapy in selected cases of:
Systemic lupus erythematosus
Acute rheumatic carditis
4. Dermatologic diseases
Pemphigus
Severe erythema multiforme (Stevens-Johnson syndrome)
Exfoliative dermatitis
Bullous dermatitis herpetiformis
Severe seborrheic dermatitis
Severe psoriasis
Mycosis fungoides
5. Allergic states
Control of severe or incapacitating allergic conditions intractable to adequate
trials of conventional treatment in:
Bronchial asthma
Contact dermatitis
Atopic dermatitis
Serum sickness
Seasonal or perennial allergic rhinitis
Drug hypersensitivity reactions
Urticarial transfusion reactions
Acute noninfectious laryngeal edema (epinephrine is the drug of first choice)
6. Ophthalmic diseases
Severe acute and chronic allergic and inflammatory processes involving the eye,
such as:
Herpes zoster ophthalmicus
Iritis, iridocyclitis
Chorioretinitis
Diffuse posterior uveitis and choroiditis
Optic neuritis
Sympathetic ophthalmia
Anterior segment inflammation
Allergic conjunctivitis
Keratitis

Allergic corneal marginal ulcers

7. Gastrointestinal diseases
To tide the patient over a critical period of the disease in:
Ulcerative colitis (Systemic therapy)
Regional enteritis (Systemic therapy)
8. Respiratory diseases
Symptomatic sarcoidosis
Berylliosis
Fulminating or disseminated pulmonary tuberculosis when used concurrently
with appropriate antituberculous chemotherapy
Loeffler's syndrome not manageable by other means
Aspiration pneumonitis
9. Hematologic disorders
Acquired (autoimmune) hemolytic anemia
Idiopathic thrombocytopenic purpura in adults (I.V. only: I.M administration is
contraindicated)
Secondary thrombocytopenia in adults
Erythroblastopenia (RBC anemia)
Congenital (erythroid) hypoplasticanemia
10. Neoplastic diseases
For palliative management of:
Leukemias and lymphomas in adults
Acute leukemia of childhood
11. Edematous states
To induce diuresis or remission of proteinuria in the nephrotic syndrome,
without uremia, of the idiopathic type, or that due to lupus erythematosus
12. Miscellaneous
Tuberculous meningitis with subarachnoid block or impending block when used
concurrently with appropriate antituberculous chemotherapy
Trichinosis with neurologic or myocardial involvement
13. Diagnostic testing of adrenocortical hyperfunction
14. Cerebral Edema associated with primary or metastatic brain tumor, craniotomy,
or head injury. Use in cerebral edema is not a substitute for careful neurosurgical
evaluation and
definitive management such as neurosurgery or other
specific therapy.
2. By intra-articular or soft tissue injection:
As adjunctive therapy for short-term administration (to tide the patient over an
acute episode or exacerbation) in:
Synovitis of osteoarthritis
Rheumatoid arthritis
Acute and subacute bursitis
Acute gouty arthritis
Epicondylitis

Acute nonspecific tenosynovitis

Post-traumatic osteoarthritis.
3. By intralesional injection:
Keloids
Localized hypertrophic, infiltrated, inflammatory lesions of: lichen planus,
psoriatic plaques, granuloma annulare and lichen simplex chronicus
(neurodermatitis)
Discoid lupus erythematosus
Necrobiosis lipoidica diabeticorum
Alopecia areata
May also be useful in cystic tumors of an aponeurosis or tendon (ganglia).

Contraindications
Systemic fungal infections. (See WARNINGS regarding amphotericin B)
Hypersensitivity to any component of this product, including sulfites (see
WARNINGS).

Warnings
Because rare instances of anaphylactoid reactions have occurred in patients
receiving parenteral corticosteroid therapy, appropriate precautionary measures
should be taken prior to administration, especially when the patient has a history of
allergy to any drug. Anaphylactoid and hypersensitivity reactions have been
reported for Dexamethasone Sodium Phosphate Injection, USP (see ADVERSE
REACTIONS). Dexamethasone Sodium Phosphate Injection, USP contains sodium
bisulfite, a sulfite that may cause allergic-type reactions including
anaphylactic symptoms and life-threatening or less severe asthmatic episodes in
certain susceptible people. The overall prevalence of sulfite sensitivity in the
general population is unknown and probably low. Sulfite sensitivity is seen more
frequently in asthmatic than in nonasthmatic people. Corticosteroids may
exacerbate systemic fungal infections and therefore should not be used in the
presence of such infections unless they are needed to control drug reactions due to
amphotericin B. Moreover, there have been cases reported in which concomitant
use of amphotericin B and hydrocortisone was followed by cardiac enlargement
and congestive failure. In patients on corticosteroid therapy subjected to any
unusual stress, increased dosage of rapidly acting corticosteroids before, during,
and after the stressful situation is indicated. Drug-induced secondary adrenocortical
insufficiency may result from too rapid withdrawal of corticosteroids and may be
minimized by gradual reduction of dosage. This type of relative insufficiency may
persist for months after discontinuation of therapy; therefore, in any situation of
stress occurring during that period, hormone therapy should be reinstituted. If the

patient is receiving steroids already, dosage may have to be increased. Since

mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid
should be administered concurrently. Corticosteroids may mask some signs of
infection, and new infections may appear during their use. There may be decreased
resistance and inability to localize infection when corticosteroids are used.
Moreover, corticosteroids may affect the nitroblue-tetrazolium test for bacterial
infection and produce false negative results. In cerebral malaria, a double-blind
trial has shown that the use of corticosteroids is associated with prolongation of
coma and a higher incidence of pneumonia and gastrointestinal bleeding.
Corticosteroids may activate latent amebiasis. Therefore, it is recommended that
latent or active amebiasis be ruled out before initiating corticosteroid therapy in
any patient who has spent time in the tropics or any patient with unexplained
diarrhea. Prolonged use of corticosteroids may produce posterior subcapsular
cataracts, glaucoma with possible damage to the optic nerves, and may enhance the
establishment of secondary ocular infections due to fungi or viruses.
Average and large doses of cortisone or hydrocortisone can cause elevation of
blood pressure, salt and water retention, and increased excretion of potassium.
These effects are less likely to occur with the synthetic derivatives except when
used in large doses. Dietary salt restriction and potassium supplementation may be
necessary. All corticosteroids increase calcium excretion. Administration of live
virus vaccines, including smallpox, is contraindicated in individuals receiving
immunosuppressive doses of corticosteroids. If inactivated viral or bacterial
vaccines are administered to individuals receiving immunosuppressive doses of
corticosteroids, the expected serum antibody response may not be obtained.
However, immunization procedures may be undertaken in patients who are
receiving corticosteroids as replacement therapy, e.g., for Addison's disease.
Persons who are on drugs which suppress the immune system are more susceptible
to infections than healthy individuals. Chickenpox and measles, for example, can
have a more serious or even fatal course in non-immune children or adults on
corticosteroids. In such children or adults who have not had these diseases,
particular care should be taken to avoid exposure. How the dose, route and
duration of corticosteroid administration affects the risk of developing a
disseminated infection is not known. The contribution of the underlying disease
and/or prior corticosteroid treatment to the risk is also not known. If exposed to
chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be
indicated. If exposed to measles, prophylaxis with pooled intramuscular
immunoglobulin (IG) may be indicated. (See the respective package inserts for
complete VZIG and IG prescribing information). If chickenpox develops,
treatment with antiviral agents may be considered.
The use of Dexamethasone Sodium Phosphate Injection, USP in active tuberculosis
should be restricted to those cases of fulminating or disseminated tuberculosis in
which the corticosteroid is used for the management of the disease in conjunction
with an appropriate antituberculous regimen. If corticosteroids are indicated in
patients with latent tuberculosis or tuberculin reactivity, close observation is
necessary as reactivation of the disease may occur. During prolonged corticosteroid

therapy, these patients should receive chemoprophylaxis. Literature reports suggest

an apparent association between use of corticosteroids and left ventricular free wall
rupture after a recent myocardial infarction; therefore, therapy with corticosteroids
should be used with great caution in these patients.
Usage in pregnancy. Since adequate human reproduction studies have not been
done with corticosteroids, use of these drugs in pregnancy or in women of
childbearing potential requires that the anticipated benefits be weighed against the
possible hazards to the mother and embryo or fetus. Infants born of mothers who
have received substantial doses of corticosteroids during pregnancy should be
carefully observed for signs of hypoadrenalism. Corticosteroids appear in breast
milk and could suppress growth, interfere with endogenous corticosteroid
production, or cause other unwanted effects. Mothers taking pharmacologic doses
of corticosteroids should be advised not to nurse.

Precautions
General
This product, like many other steroid formulations, is sensitive to heat. Therefore,
it should not be autoclaved when it is desirable to sterilize the exterior of the vial.
Following prolonged therapy, withdrawal of corticosteroids may result in
symptoms of the corticosteroid withdrawal syndrome including fever, myalgia,
arthralgia, and malaise. This may occur in patients even without evidence of
adrenal insufficiency. There is an enhanced effect of corticosteroids in patients with
hypothyroidism and in those with cirrhosis. Corticosteroids should be used
cautiously in patients with ocular herpes simplex for fear of corneal perforation.
The lowest possible dose of corticosteroid should be used to control the condition
under treatment, and when reduction in dosage is possible, the reduction must be
gradual. Psychic derangements may appear when corticosteroids are used, ranging
from euphoria, insomnia, mood swings, personality changes, and severe depression
to frank psychotic manifestations. Also, existing emotional instability or psychotic
tendencies may be aggravated by corticosteroids.
Aspirin should be used cautiously in conjunction with corticosteroids in
hypoprothrombinemia. Steroids should be used with caution in nonspecific
ulcerative colitis, if there is a probability of impending perforation, abscess or other
pyogenic infection, also in diverticulitis, fresh intestinal anastomoses, active or
latent peptic ulcer, renal insufficiency, hypertension, osteoporosis, and myasthenia
gravis. Signs of peritoneal irritation following gastrointestinal perforation in
patients receiving large doses of corticosteroids may be minimal or absent. Fat
embolism has been reported as a possible complication of hypercortisonism. When
large doses are given, some authorities advise that antacids be administered
between meals to help to prevent peptic ulcer. Growth and development of infants
and children on prolonged corticosteroid therapy should be carefully followed.
Steroids may increase or decrease motility and number of spermatozoa in some
patients. Phenytoin, phenobarbital, ephedrine, and rifampin may enhance the

metabolic clearance of corticosteroids resulting in decreased blood levels and

lessened physiologic activity, thus requiring adjustment in corticosteroid dosage.
These interactions may interfere with dexamethasone suppression tests which
should be interpreted with caution during administration of these drugs. False
negative results in the dexamethasone suppression test (DST) in patients being
treated with indomethacin have been reported. Thus, results of the DST should be
interpreted with caution in these patients. The prothrombin time should be checked
frequently in patients who are receiving corticosteroids and coumarin
anticoagulants at the same time because of reports that corticosteroids have altered
the response to these anticoagulants. Studies have shown that the usual effect
produced by adding corticosteroids is inhibition of response to coumarins, although
there have been some conflicting reports of potentiation not substantiated by
studies. When corticosteroids are administered concomitantly with potassiumdepleting diuretics, patients should be observed closely for development of
hypokalemia. Intra-articular injection of a corticosteroid may produce systemic as
well as local effects. Appropriate examination of any joint fluid present is
necessary to exclude a septic process. A marked increase in pain accompanied by
local swelling, further restriction of joint motion, fever and malaise is suggestive of
septic arthritis. If this complication occurs and the diagnosis of sepsis is confirmed,
appropriate antimicrobial therapy should be instituted. Injection of a steroid into an
infected site is to be avoided. Corticosteroids should not be injected into unstable
joints. Patients should be impressed strongly with the importance of not overusing
joints in which symptomatic benefit has been obtained as long as the inflammatory
process remains active. Frequent intra-articular injection may result in damage to
joint tissues. The slower rate of absorption by intramuscular administration should
be recognized.
Information for Patients
Persons who are on immunosuppressant doses of corticosteroids should be warned
to avoid exposure to chickenpox or measles. Patients should also be advised that if
they are exposed, medical advice should be sought without delay.

Adverse Reactions
Fluid and electrolyte disturbances
Sodium retention
Fluid retention
Congestive heart failure in susceptible patients
Potassium loss
Hypokalemic alkalosis
Hypertension
Musculoskeletal
Muscle weakness
Steroid myopathy

Loss of muscle mass

Osteoporosis
Vertebral compression fractures
Aseptic necrosis of femoral and humeral heads
Pathologic fracture of long bones
Tendon rupture
Gastrointestinal
Peptic ulcer with possible subsequent perforation and hemorrhage
Perforation of the small and large bowel, particularly in patients with
inflammatory bowel disease
Pancreatitis
Abdominal distention
Ulcerative esophagitis
Dermatologic
Impaired wound healing
Thin fragile skin
Petechiae and ecchymoses
Erythema
Increased sweating
May suppress reactions to skin tests
Burning or tingling, especially in the perineal area (after I.V. injection)
Other cutaneous reactions, such as allergic dermatitis, urticaria, angioneurotic
edema
Neurologic
Convulsions
Increased intracranial pressure with papilledema (pseudotumor cerebri) usually
after treatment
Vertigo
Headache
Psychic disturbances
Endocrine
Menstrual irregularities
Development of cushingoid state
Suppression of growth in children
Secondary adrenocortical and pituitary unresponsiveness, particularly in times of
stress, as in trauma, surgery, or illness
Decreased carbohydrate tolerance
Manifestations of latent diabetes mellitus
Increased requirements for insulin or oral hypoglycemic agents in diabetics
Hirsutism

Ophthalmic
Posterior subcapsular cataracts
Increased intraocular pressure
Glaucoma
Exophthalmos
Metabolic
Negative nitrogen balance due to protein catabolism
Cardiovascular
Myocardial rupture following recent myocardial infarction (see WARNINGS).
Other
Anaphylactoid or hypersensitivity reactions
Thromboembolism
Weight gain
Increased appetite
Nausea
Malaise
Hiccups
The following additional adverse reactions are related to parenteral
corticosteroid therapy:
Rare instances of blindness associated with intralesional therapy around the face
and head
Hyperpigmentation or hypopigmentation
Subcutaneous and cutaneous atrophy
Sterile abscess
Postinjection flare (following intra-articular use)
Charcot-like arthropathy

Overdosage
Reports of acute toxicity and/or death following overdosage of glucocorticoids are
rare. In the event of overdosage, no specific antidote is available; treatment is
supportive and symptomatic.
The oral LD50 of dexamethasone in female mice was 6.5 g/kg. The intravenous
LD50 of dexamethasone sodium phosphate in female mice was 794 mg/kg.

Dosage and Administration

Dexamethasone Sodium Phosphate Injection, USP, 4 mg/mL -- For intravenous,
intramuscular, intra-articular, intralesional, and soft tissue injection.
Dexamethasone Sodium Phosphate Injection, USP can be given directly from the
vial, or it can be added to Sodium Chloride Injection or Dextrose Injection and

administered by intravenous drip.

Solutions used for intravenous administration or further dilution of this product
should be preservative-free when used in the neonate, especially the premature
infant.
When it is mixed with an infusion solution, sterile precautions should be observed.
Since infusion solutions generally do not contain preservatives, mixtures should be
used within 24 hours.
DOSAGE REQUIREMENTS ARE VARIABLE AND MUST BE
INDIVIDUALIZED ON THE BASIS OF THE DISEASE AND THE RESPONSE
OF THE PATIENT.
Intravenous and Intramuscular Injection
The initial dosage of Dexamethasone sodium phosphate injection varies from 0.5
to 9 mg a day depending on the disease being treated. In less severe diseases doses
lower than 0.5 mg may suffice, while in severe diseases doses higher than 9 mg
may be required. The initial dosage should be maintained or adjusted until the
patient's response is satisfactory. If a satisfactory clinical response does not occur
after a reasonable period of time, discontinue Dexamethasone Sodium Phosphate
Injection, USP and transfer the patient to other therapy.
After a favorable initial response, the proper maintenance dosage should be
determined by decreasing the initial dosage in small amounts to the lowest dosage
that maintains an adequate clinical response. Patients should be observed closely
for signs that might require dosage adjustment, including changes in clinical status
resulting from remissions or exacerbations of the disease, individual drug
responsiveness, and the effect of stress (e.g., surgery, infection, trauma). During
stress it may be necessary to increase dosage temporarily. If the drug is to be
stopped after more than a few days of treatment, it usually should be withdrawn
gradually. When the intravenous route of administration is used, dosage usually
should be the same as the oral dosage. In certain overwhelming, acute, lifethreatening situations, however, administration in dosages exceeding the usual
dosages may be justified and may be in multiples of the oral dosages. The slower
rate of absorptio

Injeksi Deksametason
Fornas hal 94
Tiap 4 ml mengandung :
Dexamethason Natrium fosfat 10 mg
Na Benzoat 0,5 %
Aqua p.i ad 4 ml
Latar belakang pemilihan formula :

a. Dexamethason Natrium fosfat digunaka karena mudah larut larut dala air
sedangkan dexametason praktis tidak larut dalam air, karena sediaan injeksi
akan dibuat menggunakan air sebagai pelarut
b. Digunakan aqua pi suatu pembawa yang berfungsi sebagai pelarut.
c. Pengawet yang digunakan adalah Na. Benzoat yang berfungsi sebagai
antimikroba. Digunakan pengawet karena injeksi dalam wadah vial
pengambilannya berulang dan mudah terkontaminasi dengan udara. Na. Benzoat
dengan pH 8,0 bisa untuk mempertahankan pH zat aktif.
d. Dosis Dexamethason Natrium Fosfat dipilih 10 mg ditujukan kepada penderita
edema serebral (0,5-24 mg/hari)
e. Sterilisasi pada Dexamethason Natrium Fosfat digunakan dengan cara filtrasi
karena stabilitas dexamethason tidak tahan panas atau tidak stabil
Dibuat 8 vial vial 4 ml :
V = vol + ( 10-30% )
= (8 x 4 ml) + (30% x 8 x 4 ml)
= 41,6 ml ~ 45 ml
Dex. Na. fosfat = 45 ml x 10 mg = 112,5 mg
4 ml
Na. Benzoat = 0,5 x 45 ml = 0,255 g
100
Aqua pi = 45 ml (0,1125 + 0,255)
= 44,6325 ml

EVALUASI DAN PENYIMPANAN SEDIAAN

INJEKSI
Evaluasi
Dilakukan setelah sediaan disterilkan dan sebelum wadah dipasang etiket dan dikemas

EVALUASI FISIKA
1.

Penetapan pH . (FI ed. IV, hal 1039-1040)

2.

Bahan Partikulat dalam Injeksi <751> ( FI> ed IV, hal. 981-984).

2. Penetapan Volume Injeksi Dlam Wadah <1131> (FI ed. IV Hal 1044).
3. Uji Keseragaman Bobot dan Keseragaman Volume (FI ed III hal. 19)
4. Uji Kejernihan Larutan (FI ED. IV, hal 998)
5. Uji Kebocoran (Goeswin Agus, Larutan Parenteral)

Pada pembuatan kecil-kecilan hal ini dapat dilakukan dengan mata tetapi untuk
produksi skala besar hal ini tidak mungkin dikerjakan.
-

Wadah-wadah takaran tunggal yang masih panas setelah selesai disterilkan dimasukkan
kedalam larutan biru metilen 0,1%. Jika ada wadah-wadah yang bocor maka larutan biru
metilen akan dimasukkan kedalamnya karena perbedaan tekanan di luar dan di dalam
wadah tersebut. Cara ini tidak dapat dilakukan untuk larutan-larutan yang sudah berwarna.

Wadah-wadah takaran tunggal disterilkan terbalik, jika ada kebocoran maka larutan ini
akan keluar dari dalam wadah. Wadah-wadah yang tidak dapat disterilkan, kebocorannya
harus diperiksa dengan memasukkan wadah-wadah tersebut ke dalam eksikator yang
divakumkan. Jika ada kebocoran akan diserap keluar.
6. Uji Kejernihan dan Warna ( Goeswin Agus, Larutan Parenteral, HAL 201)
Umumnya setiap larutan suntik harus jernih dan bebas dari kotoran-kotoran. Uji ini
sangat sulit dipenuhi bila dilakukan pemeriksaan yang sangat teliti karena hampir tidak ada
larutan jernih. Oleh sebab itu untuk uji ini kriterianya cukup jika dilihat dengan mata biasa
saja yaitu menyinari wadah dari samping dengan latar belakang berwarna hitam dan putih.

Latar belakang warna hitam dipakai untuk menyelidiki kotoran-kotoran berwarna muda,
sedangkan latar belakang putih untuk menyelidiki kotoran-kotoran berwarna gelap.

EVALUASI BIOLOGI
1. Uji Efektivitas Pengawet Antimikroba <61> (FI ed IV, HAL 854-855)
2. Uji Sterilitas <71> (FI ed. IV, HAL 855-863)
3. Uji Endotoksin Bakteri <201> (FI ed. IV, HAL 905-907)
4. Uji Pirogen <231> (FI ed. IV, HAL. 908-909)
5. Uji Kandungan Zat Antimikroba <441> (FI ed. IV, HAL. 939-942)

EVALUASI KIMIA
1 Uji Identifikasi (Sesuai dengan monografi sediaan masing-masing)
2. Penetapan Kadar (Sesuai dengan monografi sediaan masing-masing).

Wadah
Wadah untuk injeksi termasuk penutup tidak boleh berinteraksi melalui berbagai cara
baik secara fisik maupun kimiawi dengan sediaan, yang dapat mengubah kekuatan, mutu
atau kemurnian di luar persyaratan resmi dalam kondisi biasa pada waktu penanganan,
pengangkutan, penyimpanan, penjualan, dan penggunaan. Wadah terbuat dari bahan yang
dapat mempermudah pengamatan terhadap isi. Tipe kaca yang dianjurkan untuk tiap
sediaan umumnya tertera dalam masing-masing monografi. (FI Ed. IV, hal 10).
Wadah dan sumbatnya tidak boleh mempengaruhi bahan yang disimpan di dalamnya
baik secara kimia maupun secara fisika, yang dapat mengakibatkan perubahan khasiat, mutu
dan kemurniannya. (FI ed. III, hal XXXIV)
Bagaimanapun bentuk dan komposisi wadah, wadah pengemas merupakan sumber dari
masalah stabilitas sediaan, bahan partikulat, dan sumber pirogen. (Diktat Steril, hal 82)
Keuntungan wadah gelas (Diktat steril, hal 82-99) :
1.

mempunyai daya tahan kimia yang baik sehingga tidak bereaksi dengan kandungan wadah
dan tidak mengabsorbsi atau mengeluarkan senyawa organik.

2.

Bersifat tidak permeable sehingga apabila ditutup dengan baik maka pemasukan atau
hilangnya gas-gas dapat diabaikan.

3.

Wadah gelas mudah dicuci karena permukannya licin

4.

Bersifat transparan sehingga dapat diamati kandungnnya dalam wadah.

5.

Mempunyai sifat kaku, kuat dan bentuknya stabil. Tahan terhadap tusukan dapat
divakumkan, dapat dipanaskan pada suhu 121O C pada sterilisasi uap dan 2600 C pada
sterilisasi kering tanpa mengalami perubahan bentuk.
Kerugian :
mudah pecah dan bobotnya relatif berat.

Wadah yang biasa digunakan untuk sedian injeksi adalah berupa vial atau ampul. Untuk
zat aktif yang mudah teroksidasi biasanya digunakan ampul berwarna gelap (biasanya
coklat) untuk melindungi sediaan dari cahaya.
Gelas tipe I untuk membuat wadah tiup dalam bentuk tabung, misalnya vial, ampul,
badan alat suntik (syringe) dan bagian infus set. Beberapa sediaan parenteral volume kecil
dikemas dalam alat suntik gelas sekali pakai (disposable one-trip glass syringe).

Penandaan (FI Ed. IV, hal 11)

Pada etiket tertera nama sediaan, untuk sediaan cair tertera persentase atau jumlah
zat aktif dalam volume tertentu, cara pemberian, kondisi penyimpanan dan tanggal
kadaluarsa, nama pabrik pembuat dan atau pengimpor serta nomor lot atau bets yang
menunjukkan identitas. Nomor lot dan nomor bets dapat memberikan informasi tentang
riwayat pembuatan lengkap meliputi seluruh proses pengolahan, sterilisasi, pengisian,
pengemasan, dan penandaan.
Bila dalam monografi tertera berbagai kadar zat aktif dalam sediaan parenteral
volume besar, maka kadar masing-masing komponen disebut dengan nama umum misalnya
injeksi Dekstrosa 5% atau Injeksi Dekstrosa (5%).
Bila formula lengkap tidak tertera dalam masing-masing monografi, Penandaan
mencakup informasi berikut :
1.

Untuk sediaan cair, persentase isi atau jumlah tiap komponen dalam volume

tertentu, kecuali bahan yang ditambahkan untuk penyesuaian pH atau untuk membuat
larutan isotonik, dapat dinyatakan nama dan efek bahan tersebut

2.

Sediaan kering atau sediaan yang memerlukan pengenceran sebelum digunakan,

jumlah tiap komponen, komposisi pengencer yang dianjurkan, jumlah yang diperlukan
untuk mendapat konsentrasi tertentu zat aktif dan volume akhir larutan yang diperoleh ,
uraian singkat pemerian larutan terkonstitusi, cara penyimpanan dan tanggal kadualarsa.
Pemberian etiket pada wadah sedemikian rupa sehingga sebagian wadah tidak
tertutup oleh etiket, untuk mempermudah pemeriksaan isi secara visual.

Pengemasan dan Penyimpanan

Volume injeksi wadah dosis tunggal dapat memberikan jumlah tertentu untuk
pemakaian parenteral sekali pakai dan tidak ada yang memungkinkan pengambilan isi dan
pemberian 1 liter. (FI Ed. IV, Hal 11)
Untuk penyimpanan obat harus disimpan sehingga tercegah cemaran dan
penguraian, terhindar pengaruh udara, kelembaban, panas dan cahaya.
Kondisi penyimpanan tergantung pada sediaannya, misalnya kondisi harus disimpan
terlindung cahaya, disimpan pada suhu kamar, disimpan di tempat sejuk, disimpan di
temapat dingin (FI Ed. III, Hal XXXIV)

CONTOH SEDIAAN DI PUSTAKA

Trissel, 10th ed.